Recent advances in knowledge about gene structure derived from the human genome project has also revealed data on genomic variation and their possible impact on complex and acute diseases as well as pharmacotherapy. The hypothesis of a genetic predisposition for complex diseases such as pain syndromes, side effects, and adverse outcomes challenging the clinician is ready to be tested by advanced genetic-epidemiologic study designs employing the latest genotyping technology. In pain therapy, the genetic background of the efficacy of analgesics, especially of opioids, is of particular interest. Genetic differences in drug kinetics and dynamics, e.g., differences in metabolism or genetic variations of the drug target (e.g., receptors) will be of importance in the future. Pharmacogenetics can individualize pharmacotherapy and improve care by predicting the optimal dose and avoiding side effects and toxicity in individual patients.